Effect of Downstream
Sequence on the Cleavage of Envelop Protein 1 Signal Sequence in Hepatitis C
Virus
ZHU Li-Xin, KONG Yu-Ying, WANG Yuan*, LI Guang-Di*
( Institute of Biochemistry and Cell Biology, Shanghai Institutes for
Biological Sciences, the Chinese Academy of Sciences, Shanghai 200031,
China )
Abstract The RNA
genome of hepatitis C virus encodes a polyprotein of ～3 000 amino acids, which is
processed into 10 viral proteins by proteases provided by host cells and virus
itself. Multiple precursors are produced due to inefficient processing. Here,
the study of E1 signal sequence (C/E1 site) processing in eukaryotic vaccinia
virus/T7 system is reported. Differently truncated HCV structural proteins were
expressed in this system. It was found that the efficient cleavage of E1 signal
sequence was affected by downstream envelop protein sequences. When the lacZ
gene encoding a product with similar size was engineered downstream to the E1
signal sequence, the inefficient cleavage of signal sequence was also observed,
suggesting that the effect of downstream sequence on the cleavage was due to
the presence of the envelop protein sequences. Computer-aided analysis clearly
showed that E1 signal sequences was a typical signal sequence. The in fluence
of downstream sequences to signal sequence cleavage demonstrated here was
uncommon. To date, similar observations were only reported for the processing
of IL-12 signal sequence and the C/prM site of flavivirus. As both flavivirus
and HCV are classified into the same Flaviviridae family, this
downstream-sequence-related cleavage of signal sequence worths further
studying.
Key words hepatitis C virus (HCV)； E1； signal sequence； post-translational processing
*Corresponding authors： Tel, 86-21-64374430； Fax, 86-21-64338357； e-mail, [email protected]